Our goals are to establish the mechanism(s) by which a series of xanthine derivatives alter the contraction of muscular tissues. The xanthines to be studied are potent inhibitors of cyclic nucleotide phosphodiesterase activities and some are relatively selective inhibitors of cyclic AMP or cyclic GMP hydrolysis by the phosphodiesterases of the tissues being studied. We will use these phosphodiesterase inhibitors as tools to help define the roles of the cyclic nucleotides in these tissues if it can be established that the pharmacological effects of these agents arise from their inhibition of phosphodiesterases. The specific objectives of this study are: (1) to determine the potency of new phosphodiesterase inhibitors to alter the contraction of smooth, cardiac and skeletal muscle, (2) to quantitate the ability of these phosphodiesterase inhibitors to alter the extent of activation of cyclic AMP-dependent protein kinases and the levels of cyclic GMP in these tissues (3) to determine the ability of these agents to alter Ca ions uptake and release by subcellular vesicle preparations from these tissues, and (4) to determine the potency of these agents to interact with (potentiate, inhibit or be additive with) the effect of beta-adrenergic agonists, purinergic agonists, and sodium nitroprusside on coronary artery strips.